Schematic overview of the cellular and molecular mechanisms involved in the cancer progression, including the proposed cellular and molecular mechanisms in cancer cells trajectory. AT1: alveolar type 1 cells; AT2: alveolar type 2 cells; AAH: atypical adenomatous hyperplasia; AIS: adenocarcinoma in situ; MIA: minimally invasive adenocarcinoma; IA: invasive adenocarcinoma; EMT: epithelial-mesenchymal transition

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	Gene summary
	Malignant transformation analysis
	Malignant transformation related pathway analysis
	Cell-cell communication analysis
	Single-cell gene regulatory network inference analysis
	Somatic mutation of malignant transformation related genes
	Related drugs of malignant transformation related genes

Gene: NXT2

Gene summary for NXT2

Gene summary.

Gene information	Species	Human
	Gene symbol	NXT2
	Gene ID	55916
	Gene name	nuclear transport factor 2 like export factor 2
	Gene Alias	P15-2
	Cytomap	Xq23
	Gene Type	protein-coding
	GO ID	GO:0006403
	UniProtAcc	Q9NPJ8

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Malignant transformation analysis

Identification of the aberrant gene expression in precancerous and cancerous lesions by comparing the gene expression of stem-like cells in diseased tissues with normal stem cells

Malignant transformation involving gene list.

Entrez ID	Symbol	Replicates	Species	Organ	Tissue	Adj P-value	Log2FC	Malignancy
55916	NXT2	LZE4T	Human	Esophagus	ESCC	1.89e-04	1.41e-01	0.0811
55916	NXT2	LZE5T	Human	Esophagus	ESCC	7.99e-03	4.49e-01	0.0514
55916	NXT2	LZE7T	Human	Esophagus	ESCC	5.25e-03	1.54e-01	0.0667
55916	NXT2	LZE8T	Human	Esophagus	ESCC	1.04e-08	3.55e-01	0.067
55916	NXT2	LZE22T	Human	Esophagus	ESCC	1.09e-02	4.97e-01	0.068
55916	NXT2	LZE24T	Human	Esophagus	ESCC	6.72e-11	2.76e-01	0.0596
55916	NXT2	P2T-E	Human	Esophagus	ESCC	4.55e-17	3.78e-01	0.1177
55916	NXT2	P4T-E	Human	Esophagus	ESCC	5.81e-07	2.50e-01	0.1323
55916	NXT2	P5T-E	Human	Esophagus	ESCC	2.16e-08	8.21e-02	0.1327
55916	NXT2	P8T-E	Human	Esophagus	ESCC	7.74e-20	4.23e-01	0.0889
55916	NXT2	P9T-E	Human	Esophagus	ESCC	3.72e-04	1.54e-01	0.1131
55916	NXT2	P10T-E	Human	Esophagus	ESCC	2.45e-07	1.78e-01	0.116
55916	NXT2	P11T-E	Human	Esophagus	ESCC	2.10e-03	2.10e-01	0.1426
55916	NXT2	P12T-E	Human	Esophagus	ESCC	7.10e-05	1.40e-01	0.1122
55916	NXT2	P15T-E	Human	Esophagus	ESCC	7.00e-08	1.39e-01	0.1149
55916	NXT2	P16T-E	Human	Esophagus	ESCC	9.20e-18	3.34e-01	0.1153
55916	NXT2	P17T-E	Human	Esophagus	ESCC	1.17e-12	8.23e-01	0.1278
55916	NXT2	P20T-E	Human	Esophagus	ESCC	2.04e-09	1.49e-01	0.1124
55916	NXT2	P21T-E	Human	Esophagus	ESCC	1.51e-07	1.68e-01	0.1617
55916	NXT2	P22T-E	Human	Esophagus	ESCC	2.68e-16	2.04e-01	0.1236

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ

∗log2FC in expression of this searched gene in stem-like cells from each diseased tissue sample relative to stem-like cells in normal samples in each tissue plotted against the malignancy continuum. Samples are colored based on if they are from different disease stage.

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Malignant transformation related pathway analysis

Find out the enriched GO biological processes and KEGG pathways involved in transition from healthy to precancer to cancer

Figure of enriched GO biological processes.

Tissue	Disease Stage	Enriched GO biological Processes
Colorectum	AD
Colorectum	SER
Colorectum	MSS
Colorectum	MSI-H
Colorectum	FAP

∗Top 15 enriched GO BP terms are showed in the bar plot of each disease state in each tissue. Each row represents a significant GO biological process which is colored according to the -log10(p.adjust).

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Enriched GO biological processes.

GO ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	Count
GO:0072594110	Esophagus	ESCC	establishment of protein localization to organelle	311/8552	422/18723	3.02e-32	2.13e-29	311
GO:0006913110	Esophagus	ESCC	nucleocytoplasmic transport	230/8552	301/18723	6.04e-28	2.02e-25	230
GO:0051169110	Esophagus	ESCC	nuclear transport	230/8552	301/18723	6.04e-28	2.02e-25	230
GO:0006403110	Esophagus	ESCC	RNA localization	166/8552	201/18723	1.95e-27	6.18e-25	166
GO:003450418	Esophagus	ESCC	protein localization to nucleus	211/8552	290/18723	4.06e-21	6.60e-19	211
GO:005123617	Esophagus	ESCC	establishment of RNA localization	134/8552	166/18723	1.23e-20	1.81e-18	134
GO:005102815	Esophagus	ESCC	mRNA transport	110/8552	130/18723	2.76e-20	3.80e-18	110
GO:005065717	Esophagus	ESCC	nucleic acid transport	131/8552	163/18723	6.94e-20	8.46e-18	131
GO:005065817	Esophagus	ESCC	RNA transport	131/8552	163/18723	6.94e-20	8.46e-18	131
GO:001593117	Esophagus	ESCC	nucleobase-containing compound transport	162/8552	222/18723	9.87e-17	7.93e-15	162
GO:001703818	Esophagus	ESCC	protein import	149/8552	206/18723	5.90e-15	3.31e-13	149
GO:005117014	Esophagus	ESCC	import into nucleus	111/8552	159/18723	5.69e-10	1.44e-08	111
GO:000660613	Esophagus	ESCC	protein import into nucleus	108/8552	155/18723	1.16e-09	2.77e-08	108
GO:007259422	Liver	HCC	establishment of protein localization to organelle	299/7958	422/18723	1.06e-32	6.10e-30	299
GO:000640321	Liver	HCC	RNA localization	151/7958	201/18723	3.72e-21	5.89e-19	151
GO:000691322	Liver	HCC	nucleocytoplasmic transport	208/7958	301/18723	5.51e-21	8.12e-19	208
GO:005116922	Liver	HCC	nuclear transport	208/7958	301/18723	5.51e-21	8.12e-19	208
GO:003450421	Liver	HCC	protein localization to nucleus	194/7958	290/18723	2.84e-17	2.85e-15	194
GO:005123621	Liver	HCC	establishment of RNA localization	121/7958	166/18723	1.61e-15	1.19e-13	121
GO:005065711	Liver	HCC	nucleic acid transport	118/7958	163/18723	8.30e-15	5.60e-13	118

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05014210	Esophagus	ESCC	Amyotrophic lateral sclerosis	266/4205	364/8465	1.31e-20	2.20e-18	1.13e-18	266
hsa0301321	Esophagus	ESCC	Nucleocytoplasmic transport	89/4205	108/8465	1.20e-12	2.37e-11	1.21e-11	89
hsa0516425	Esophagus	ESCC	Influenza A	122/4205	171/8465	5.01e-09	4.79e-08	2.45e-08	122
hsa0301524	Esophagus	ESCC	mRNA surveillance pathway	72/4205	97/8465	6.12e-07	4.10e-06	2.10e-06	72
hsa0501438	Esophagus	ESCC	Amyotrophic lateral sclerosis	266/4205	364/8465	1.31e-20	2.20e-18	1.13e-18	266
hsa0301331	Esophagus	ESCC	Nucleocytoplasmic transport	89/4205	108/8465	1.20e-12	2.37e-11	1.21e-11	89
hsa0516435	Esophagus	ESCC	Influenza A	122/4205	171/8465	5.01e-09	4.79e-08	2.45e-08	122
hsa0301534	Esophagus	ESCC	mRNA surveillance pathway	72/4205	97/8465	6.12e-07	4.10e-06	2.10e-06	72
hsa0501422	Liver	HCC	Amyotrophic lateral sclerosis	252/4020	364/8465	8.85e-18	7.41e-16	4.12e-16	252
hsa03013	Liver	HCC	Nucleocytoplasmic transport	81/4020	108/8465	4.28e-09	6.83e-08	3.80e-08	81
hsa0301521	Liver	HCC	mRNA surveillance pathway	66/4020	97/8465	3.16e-05	1.88e-04	1.04e-04	66
hsa0516421	Liver	HCC	Influenza A	101/4020	171/8465	1.41e-03	5.07e-03	2.82e-03	101
hsa0501432	Liver	HCC	Amyotrophic lateral sclerosis	252/4020	364/8465	8.85e-18	7.41e-16	4.12e-16	252
hsa030131	Liver	HCC	Nucleocytoplasmic transport	81/4020	108/8465	4.28e-09	6.83e-08	3.80e-08	81
hsa0301531	Liver	HCC	mRNA surveillance pathway	66/4020	97/8465	3.16e-05	1.88e-04	1.04e-04	66
hsa0516431	Liver	HCC	Influenza A	101/4020	171/8465	1.41e-03	5.07e-03	2.82e-03	101
hsa0501428	Oral cavity	OSCC	Amyotrophic lateral sclerosis	246/3704	364/8465	6.65e-21	1.11e-18	5.67e-19	246
hsa030136	Oral cavity	OSCC	Nucleocytoplasmic transport	82/3704	108/8465	7.93e-12	1.33e-10	6.77e-11	82
hsa030158	Oral cavity	OSCC	mRNA surveillance pathway	75/3704	97/8465	1.30e-11	2.01e-10	1.02e-10	75
hsa0516418	Oral cavity	OSCC	Influenza A	116/3704	171/8465	1.23e-10	1.78e-09	9.08e-10	116

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Cell-cell communication analysis

Identification of potential cell-cell interactions between two cell types and their ligand-receptor pairs for different disease states

Ligand

Receptor

LRpair

Pathway

Tissue

Disease Stage

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Single-cell gene regulatory network inference analysis

Find out the significant the regulons (TFs) and the target genes of each regulon across cell types for different disease states

Cell Type

Tissue

Disease Stage

Target Gene

RSS

Regulon Activity

∗The dot plots of a searched regulon are shown for all cell subpopulations in each disease state of each tissue based on the regulon specific score inferred using pySCENIC and by calculating the average expression.

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Somatic mutation of malignant transformation related genes

Annotation of somatic variants for genes involved in malignant transformation

Hugo Symbol

Variant Class

Variant Classification

dbSNP RS

HGVSc

HGVSp

HGVSp Short

SWISSPROT

BIOTYPE

SIFT

PolyPhen

Tumor Sample Barcode

Tissue

Histology

Sex

Age

Stage

Therapy Types

Drugs

Outcome

NXT2

SNV

Missense_Mutation

c.415N>G

p.Gln139Glu

p.Q139E

Q9NPJ8

protein_coding

tolerated(0.29)

benign(0.043)

TCGA-A8-A09K-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NXT2

SNV

Missense_Mutation

c.149N>T

p.Thr50Ile

p.T50I

Q9NPJ8

protein_coding

deleterious_low_confidence(0.04)

benign(0)

TCGA-EW-A1IZ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

taxotere

NXT2

SNV

Missense_Mutation

c.220G>C

p.Glu74Gln

p.E74Q

Q9NPJ8

protein_coding

deleterious(0.02)

benign(0.362)

TCGA-EK-A3GK-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

NXT2

SNV

Missense_Mutation

c.458G>T

p.Gly153Val

p.G153V

Q9NPJ8

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-EK-A3GK-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

NXT2

insertion

Frame_Shift_Ins

novel

c.246_247insCTCTATAT

p.Thr83LeufsTer12

p.T83Lfs*12

Q9NPJ8

protein_coding

TCGA-DS-A1OC-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

gemcitabine

NXT2

SNV

Missense_Mutation

c.566N>G

p.Phe189Cys

p.F189C

Q9NPJ8

protein_coding

deleterious(0.01)

probably_damaging(0.981)

TCGA-AA-3494-01

Colorectum

colon adenocarcinoma

Male

<65

III/IV

Chemotherapy

folinic

NXT2

SNV

Missense_Mutation

c.107N>A

p.Arg36Gln

p.R36Q

Q9NPJ8

protein_coding

tolerated_low_confidence(0.44)

benign(0.007)

TCGA-CM-6678-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Chemotherapy

fluorouracil

NXT2

SNV

Missense_Mutation

novel

c.587N>T

p.Ser196Ile

p.S196I

Q9NPJ8

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.621)

TCGA-F5-6814-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

NXT2

SNV

Missense_Mutation

c.107N>A

p.Arg36Gln

p.R36Q

Q9NPJ8

protein_coding

tolerated_low_confidence(0.44)

benign(0.007)

TCGA-A5-A0GB-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

NXT2

SNV

Missense_Mutation

novel

c.577N>T

p.Asp193Tyr

p.D193Y

Q9NPJ8

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-A5-A2K5-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

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Related drugs of malignant transformation related genes

Identification of chemicals and drugs interact with genes involved in malignant transfromation

(DGIdb 4.0)

Entrez ID

Symbol

Category

Interaction Types

Drug Claim Name

Drug Name

PMIDs

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